This invention relates to spectroscopic methods using nuclear magnetic resonance (NMR). More specifically, the invention relates to methods for performing spatially localized NMR chemical shift spectroscopy.
Atomic nuclei having net magnetic moments placed in a static magnetic field, B.sub.o, oscillate or precess about the axis of field B.sub.o at an NMR (Larmor) frequency .omega. given by the equation EQU .omega.=.gamma.B.sub.o ( 1)
in which .gamma. is the gyro-magnetic ratio (constant for each NMR isotope). The frequency at which the nuclei precess is thus primarily dependent on the strength of the magnetic field and B.sub.o, and increases with increasing field strength. Chemical shifts occur where the NMR frequency of resonant nuclei of the same type in a given molecule differ because of different magnetic environments produced by differences in their chemical environment. For example, electrons partially screen the nucleus from the magnetic field and thereby affect its resonant frequency. The degree of shielding caused by the electrons depends on the environment of the nucleus, and thus the chemical shift spectrum of a given molecule is unique and can be used for identification. Because the resonant frequency, hence the absolute chemical shift, is dependent on the strength of the applied field, the chemical shift spectrum is expressed as fractional shift in parts-per-million (ppm) of the NMR frequency relative to an arbitrary reference compound. By way of illustration, the range of chemical shifts is about 10 ppm for protons (.sup.1 H), 30 ppm for phosphorus (.sup.31 P), and 200 ppm for carbon (.sup.13 C). In order to discern such small chemical shifts, the homogeneity of field B.sub.o must exceed the differences in chemical shifts of the peaks in the spectrum and typically is much better than 1 part in 10.sup.6 (1 ppm).
In conventional NMR spectroscopy, chemically shifted signals are observed from the whole of the NMR sample placed in the region to which the NMR coil is sensitive. While this is satisfactory for studying the chemical structure of a homogeneous sample, to enable discrimination of normal and abnormal conditions in biological or medical diagnostic applications, it is necessary to spatially discriminate the signal components. For instance, phosphorus exists in the body attached to key molecules involved in metabolism. The localized measurement of the amplitudes of the phosphorus spectral lines could provide a direct and unique measure of cellular energy and of the state of health of the tissue in the region examined.
In the past, surface coil, topical, and sensitive point NMR methods have been used to perform localized chemical shift spectroscopy. All of these techniques have limitations. In surface coil spectroscopy, a flat NMR receiver/transmitter coil is positioned over the sample region of interest. The spatial selectivity of the surface coil is, however, limited to substantially a volume subtended by the coil circumference and one radius deep from the coil center. Some variation in depth is possible by changing the NMR pulse lengths, but scanning typically requires manually moving the coil and re-tuning it. Additionally, the size of the sensitive region is limited by the coil diameter and unwanted contributions to the NMR signal from the coil leads. In topical NMR, magnetic field gradients are applied to generate a field that is homogeneous only over a small fixed volume centered on the region of interest. Since the NMR signal is observed in the presence of a gradient magnetic field, some broadening, and consequent loss of spectral resolution, of the spectra occurs. Other regions of interest may be scanned by moving the sample through the volume, a less than convenient or efficient expedient. Spatial localization in the sensitive point method is achieved by application of three orthogonal, time-dependent linear gradient magnetic fields in the presence of a continuous sequence of closely spaced phase-alternated radio frequency (RF) excitation pulses. The time-dependent NMR signal component originating outside the sensitive point is removed by a low-pass filter, leaving the time-independent signal originating only from the sensitive point. This signal is Fourier transformed with respect to the data acquisition time to yield the chemical shift spectrum. The sensitive point is scanned across a sample by changing the ratio of currents in the appropriate gradient coil set. An objectionable feature of this method is the conflicting requirement for time-dependent fields outside the volume of interest, while a homogeneous, time-independent field is required within the sensitive volume. Under these conditions, the spectra from the sensitive volume are artificially broadened and contain sideband-type artifacts which again deleteriously reduce spectral resolution.
Accordingly, it is an object of the invention to provide improved methods for performing localized spectroscopy in which the sensitive volume is selected electronically without moving parts or gantries and which minimize spectral distortion.
It is another object of the invention to provide improved localized spectroscopy methods in which the range of positions of the sensitive volume is selectable without restriction.
It is still another object of the invention to provide improved localized NMR spectroscopy methods in which the NMR signal or the free induction decay (FID) is observed in the absence of magnetic field gradients used for spatial localizaton, thereby avoiding spectral line broadening and loss of spectral resolution.